Low-dose glucocorticoids for long-term control of AAV as effective as…

A combination regimen of low-dose glucocorticoids and rituximab is just as effective in controlling ANCA-associated vasculitis (AAV) as a standard regimen of high-dose glucocorticoids and rituximab, according to data from a clinical trial of two years.

Long-term results indicate that although effectiveness is comparable, the risk of serious side effects is significantly reduced with the low-dose regimen, supporting it as a strategy.

The study, Reduced-Dose or High-Dose Glucocorticoids Added to Rituximab During Remission Induction in ANCA-Associated Vasculitis: 2-Year Prespecified Follow-up Studywas published in theAnnals of Rheumatic Diseases.

AAV is marked by the production of autoreactive antibodies, called ANCA, which cause inflammation of small blood vessels, damaging the kidneys and lungs.

Standard AAV treatment generally combines high-dose glucocorticoids, due to their rapid and potent anti-inflammatory and immunosuppressive effects, as well as immunosuppressants, such as rituximab or cyclophosphamide.

Because long-term treatment and higher doses of glucocorticoids are associated with serious side effects, reduced-dose glucocorticoid or no-glucocorticoid regimens have recently been evaluated in clinical trials, wrote Japanese researchers who have launched a phase 4 clinical trial called LoVAS (NCT02198248). ), in which people with AAV without serious lung or kidney disease were treated with rituximab plus prednisolone at 1 mg/kg/day or 0.5 mg/kg/day.

Low-dose versus high-dose glucocorticoids for AAV

After five months, prednisolone was stopped in the low-dose group and reduced to 10 mg/day in the high-dose group. Maintenance treatment with rituximab was continued for up to two years.

Sold under the names Rituxan and MabThera, and with biosimilars available, rituximab works by killing antibody-producing B cells.

The main objective of the study was to compare the extent to which the two treatment regimens could induce remission at six months. Baseline data previously showed comparable effectiveness between them, with around 70% of patients in both groups achieving this. Serious side effects were less common in the low dose group (18.8% versus 36.9%).

The long-term effects of the low-dose regimen were not known, however, leading researchers to analyze two years of data from LoVAS to compare results between the two. The analysis included data from 69 patients who received the low-dose regimen and 65 patients who received the standard regimen.

Relapse rates were slightly higher in the group receiving the standard diet (13% versus 7.6%), but the differences between groups did not reach statistical significance, meaning they were likely due to chance. . Similar results were found when the team looked only at the subgroup that achieved remission after six months.

No significant differences between groups were observed for patient-reported measures of disease activity and two-year quality of life, as well as mortality rates, with two deaths reported in the group. low dose (2.8%) and five in the high dose group. (7.6%). One case of renal failure occurred in the high dose group. None were reported in the low dose group.

Relapse rates at 24 months were not significantly different between treatment groups, and other efficacy outcomes were also not different between groups, the researchers wrote.

Among those who achieved remission after six months, 89.7% of the low-dose group were no longer taking glucocorticoids after two years, compared to only 15.5% in the standard-dose group. This suggests that once disease remission is achieved, long-term administration of glucocorticoids may not be necessary for patients treated with rituximab maintenance therapy.

Prevalence of serious side effects

Serious side effects were significantly less common in the low-dose group than in the high-dose group (27.5% vs. 46.2%), as were serious infections (10.1% vs. 24.6%). Other common glucocorticoid-related side effects, including non-serious infections, insomnia, and fractures, occurred at a significantly lower frequency in the low-dose group. The difference was particularly striking during the first months of treatment, when the risk of serious side effects is highest, the researchers said.

The percentage of patients who experienced a composite outcome of death, relapse, renal failure, and serious adverse events was comparable between the lowest dose and the standard regimen (36.2% versus 49.2%), as were the rates of cumulative survival without such events (62.7% versus 51.2%).

The results highlight that from both a short- and long-term perspective, the benefit of the reduced-dose regimen was confirmed, the scientists wrote, noting, however, that the trial was primarily designed to compare differences after six months and the sample size. may not have been large enough to detect significant differences between groups in outcomes. They also noted that the results may not be applicable to all patients, given that all participants in this trial were Japanese and most tested positive for antibodies against myeloperoxidase, one of the two most common targets of ANCA.